Parenteral Nutrition Solutions Research Articles

微量元素製剤を混注した高カロリー輸液剤中における鉄コロイドからの鉄の解離がラットヘプシジン誘導に及ぼす影響

微量元素製剤を混注した高カロリー輸液剤中における鉄コロイドからの鉄の解離がラットヘプシジン誘導に及ぼす影響

Intrauterine-Like Growth Rates Can Be Achieved with Premixed Parenteral Nutrition Solution in Preterm Infants

Growth failure in neonatal intensive care units is a major challenge for pediatricians and neonatologists. The use of early “aggressive” parenteral nutrition (PN), with >2.5 g/(kg ·d) of amino acids and at least 40 kcal/(kg ·d) of energy from the first day of life, has been shown to provide nutritional intakes in the range recommended by international guidelines, reducing nutritional deficit and the incidence of postnatal growth restriction in preterm infants. However, nutritional practices and adherence to recommendations may vary in different hospitals. Two ready-to-use (RTU), premixed parenteral solutions (PSs) designed for preterm infants have been prospectively evaluated: a binary RTU premixed PS from our hospital pharmacy and a commercially premixed 3-chamber bag (Baxter Healthcare). These premixed PSs provide nitrogen and energy intakes in the range of the most recent recommendations, reducing or eliminating the early cumulative nutritional deficit in very-low-birth-weight infants, and avoiding the development of postnatal growth restriction. A further rationale for RTU premixed PSs is that preterm infants require balanced PN that contains not only amino acids and energy but also minerals and electrolytes from the first day of life in order to reduce the incidence of metabolic disorders frequently reported in extremely-low-birth-weight infants during the early weeks of life.

A Comparison Between Customized and Premixed Parenteral Nutrition

Background. Parenteral route is accepted for delivering nutrition when enteral feeding is not possible. Standardized premixed parenteral nutrition solution (SPNS) formulations are uniform in their characteristics and can be chosen based on the same nutrient calculations. We compared the feasibility of administering SPNS as an alternative to customized parenteral nutrition solution (CPNS) and calculate its cost implications. Methods. Retrospective review of 47 patients receiving CPNS at a tertiary care hospital ICU was performed and compared with SPNS formulations. The amounts of macro- and micronutrients (days 1, 3, 5, 7) were recorded and averaged to 2000-mL bag. These data were compared with the available premixed formulations and percentage differences were calculated. The costs and manpower for CPNS were obtained from our institutional central pharmacy. Results. The percentage difference for carbohydrates and proteins ranged from −1.0% to 2.9% and 5.8% to 9.0% with an average of 0.8% and 7.0%, respectively across all days. Since premixed micronutrients were only available in one formula, they were not easily comparable. The cost analysis showed an average savings of approximately $130 per parenteral nutrition bag. Conclusions. While macronutrients are quite comparable between formulations, any required micronutrients should be managed individually. SPNS has potential cost savings compared with CPNS when applied in the right setting.

Diverse effects of parenteral arginine on systemic and local oxidant–antioxidant homeostasis and nitrosative stress in rats with subacute peritonitis

BackgroundThe beneficial effects of arginine on oxidative stress have been previously reported; however, excess production of nitric oxide, an arginine metabolite, may cause hemodynamic instability and inflammatory response. Previous studies have demonstrated that parenteral arginine levels at 2%–4% of total calories may alleviate inflammation and enhance immunity, whereas greater than 6% of total calories may have adverse effects in rats with subacute peritonitis. Herein, we investigated the effects of parenteral arginine dose on lipid peroxidation (thiobarbituric acid reactive substances, TBARS) and antioxidant enzyme activities in the plasma and organs. Materials and methodsMale Wistar rats with cecal puncture–induced subacute peritonitis were infused with parenteral nutrition solutions containing 1.61% (CP group), 2.85% (LA group), 4.08% (MA group), and 6.54% (HA group) of total calories as arginine for 7 d. Healthy, orally fed rats (NC group) were used as references. ResultsSubacute peritonitis significantly elevated the levels of nitrate, nitrite and TBARS in the plasma and decreased glutathione peroxidase activity in the kidneys. These changes were significantly reversed in the MA and HA groups. The MA and HA groups had significantly increased nitrotyrosine levels in the plasma. The LA, MA, and HA groups had significantly increased glutathione peroxidase activity in the plasma, cytochrome P450 levels in the liver, and nitrotyrosine levels in the heart and had significantly decreased TBARS levels in the kidneys compared with the CP group. ConclusionsOur results suggest that parenteral arginine at a dose less than 4% of total calories may attenuate lipid peroxidation and increase antioxidant enzyme activities without leading to nitrosative stress in subacute peritonitis.

Evaluation of Efficacy and Safety of Premixed Parenteral Nutrition versus Customized Parenteral Nutrition in a Large Teaching Hospital

In the last two decades, there has been a significant degree of controversy surrounding the use of standardized parenteral solutions. Opponents of standardized parenteral nutrition claim that individualized parenteral nutrition is necessary because the critically ill patient requires daily manipulation of macro- and micro-nutrients secondary to stress associated with complex ailments. The purpose of this study was to determine if premixed parenteral nutrition solutions were equally safe and efficacious, while being less costly, in managing parenteral nutrition of patients at a large metropolitan teaching hospital, as compared to customized parenteral nutrition solutions. This was a randomized controlled trial with no placebo involving 100 patients requiring central parenteral nutrition. Consenting patients received either customized parenteral nutrition or premixed double chamber parenteral nutrition containing protein, carbohydrates and electrolytes. Vitamins and trace elements were added as needed. Each subject enrolled in the study was followed until the parenteral nutrition was either discontinued, the patient was transferred from the facility, or the patient expired during the study. Premixed and customized parenteral nutrition solutions were shown to be equally efficacious in patients as their blood glucose, fluid status, nutritional markers, serum electrolytes, phosphate, and magnesium values were within normal limits (p<.05). Premixed parenteral nutrition is associated with significantly better safety as compared to customized parenteral nutrition (11). Furthermore, the cost difference was $41,934 when comparing the premixed formulation to the customized solution. In this study, premixed parenteral nutrition solutions were equally safe, effective, and less costly than customized parenteral nutrition formulas. Patients receiving premixed parenteral nutrition experienced less adverse drug reactions and metabolic abnormalities than patients receiving customized parenteral nutrition.

Probability‐Based Compatibility Curves for Calcium and Phosphates in Parenteral Nutrition Formulations

The information content of the calcium phosphate compatibility curves for adult parenteral nutrition (PN) solutions may benefit from a more sophisticated statistical treatment. Binary logistic regression analyses were evaluated as part of an alternate method for generating formulation compatibility curves. A commercial PN solution was challenged with a systematic array of calcium and phosphate concentrations. These formulations were then characterized for particulates by visual inspection, light obscuration, and filtration followed by optical microscopy. Logistic regression analyses of the data were compared with traditional treatments for generating compatibility curves. Assay-dependent differences were observed in the compatibility curves and associated probability contours; the microscopic method of precipitate detection generated the most robust results. Calcium and phosphate compatibility data generated from small-volume glass containers reasonably predicted the observed compatibility of clinically relevant flexible containers. The published methods for creating calcium and phosphate compatibility curves via connecting the highest passing or lowest failing calcium concentrations should be augmented or replaced by probability contours of the entire experimental design to determine zones of formulation incompatibilities. We recommend researchers evaluate their data with logistic regression analysis to help build a more comprehensive probabilistic database of compatibility information.

Excessive Aluminum Accumulation in the Bones of Patients on Long‐Term Parenteral Nutrition

Aluminum (Al) contamination of parenteral nutrition (PN) solutions remains a concern for long-term PN patients. Al accumulates particularly in bone. Excessive exposure to Al may result in increased Al body burden and impaired bone formation and mineralization, leading to bone disease. Although the U.S. Food and Drug Administration (FDA) has limited Al contamination in large-volume parenteral solutions, small-volume parenterals may still contribute considerable amounts of Al to PN solutions. The goal of this study is to determine whether or not long-term adult PN patients remain at risk for increased bone Al accumulation. We measured Al accumulation in autopsy bones from 7 patients who had received PN for 2-21 years and compared bone Al levels with those in living control patients undergoing hip or knee replacement. Electrothermal atomic absorption spectrometry was used for bone Al measurements. When compared with bone Al content in controls, markedly elevated Al levels (P < .0001) were found in the bones of all but 1 patient, who received PN for only 2 years before death. Even greater Al accumulation was found for PN patients who developed late renal impairment (P = .0159). We conclude that long-term adult PN patients continue to be at risk for Al toxicity.

Developing and implementing all-in-one standard paediatric parenteral nutrition.

Parenteral nutrition (PN) is a feeding mode suitable for children that do not achieve requirements via the enteral route. For this intervention to be successful, healthcare professionals require: knowledge on nutrient requirements; access to an aseptic compounding facility; and a system that ensures adequate and safe delivery of PN. Previously, it was thought that individualised PN was the “gold standard” for delivering nutrients to children; however, studies have highlighted concerns regarding inadequate delivery of nutrients, prescribing and compounding errors. We, therefore, set out to develop and implement all-in-one (AIO) paediatric PN solutions. Through a systematic approach, four AIO PN solutions were developed: birth–two months of age (Ped 1); two months–10 kg (Ped 2); 11–15 kg (Ped 3); and 16–30 kg (Ped 4). We implemented them with the help of a teaching pack, over a one month time period, and reviewed usage at six months. At that time, five children initially received standard PN without electrolyte changes; but after a few days, electrolytes needed amendments, and three required individualised PN. A change to AIO PN is feasible and safe; however, some may require electrolyte changes, and there will always be those that will require individualised PN.

Reformulation of standardised neonatal parenteral nutrition to improve nutrient delivery

Postnatal growth failure is common in preterm infants and one reason for this is that nutritional care is often variable and suboptimal. Achieving targets for nutrient intakes in this group...

Can ‘stock’ PN meet the requirements of the neonatal population?

AimsIn 2011, the recipes of our 3 ‘stock’ parenteral nutrition (PN) solutions were reformulated to optimise nutrition according to recommended guidelines1 2 and reduce the amount of compounded PN needed....

Validation of a once-a-week set up for an automated compounder device for parenteral nutrition solutions

BackgroundSetting up an automated compounder device (ACD) takes time and money. Daily production of paediatric parenteral nutrition (PN) solutions in our pharmacy decreased after implementing standard PN for neonatology. To...

A Metabolomic Analysis of Two Intravenous Lipid Emulsions in a Murine Model

BackgroundParenteral nutrition (PN), including intravenous lipid administration, is a life-saving therapy but can be complicated by cholestasis and liver disease. The administration of intravenous soy bean oil (SO) has been associated with the development of liver disease, while the administration of intravenous fish oil (FO) has been associated with the resolution of liver disease. The biochemical mechanism of this differential effect is unclear. This study compares SO and FO lipid emulsions in a murine model of hepatic steatosis, one of the first hits in PN-associated liver disease.MethodsWe established a murine model of hepatic steatosis in which liver injury is induced by orally feeding mice a PN solution. C57BL/6J mice were randomized to receive PN alone (a high carbohydrate diet (HCD)), PN plus intravenous FO (Omegaven®; Fresenius Kabi AG, Bad Homburg VDH, Germany), PN plus intravenous SO (Intralipid®; Fresenius Kabi AG, Bad Homburg v.d.H., Germany, for Baxter Healthcare, Deerfield, IL), or a chow diet. After 19 days, liver tissue was harvested from all animals and subjected to metabolomic profiling.ResultsThe administration of an oral HCD without lipid induced profound hepatic steatosis. SO was associated with macro- and microvesicular hepatic steatosis, while FO largely prevented the development of steatosis. 321 detectable compounds were identified in the metabolomic analysis. HCD induced de novo fatty acid synthesis and oxidative stress. Both FO and SO relieved some of the metabolic shift towards de novo lipogenesis, but FO offered additional advantages in terms of lipid peroxidation and the generation of inflammatory precursors.ConclusionsImproved lipid metabolism combined with reduced oxidative stress may explain the protective effect offered by intravenous FO in vivo.

Clinical experience with a lipid‐free, ready‐made parenteral nutrition solution in dogs: 70 cases (2006–2012)

To review the clinical use of a lipid-free, ready-made amino acid and glucose parenteral nutrition (PN) solution in dogs. Retrospective study of dogs from 2006 to 2012 that received this form of PN. University veterinary teaching hospital. Seventy dogs presented to the hospital for treatment of various diseases in which PN was used as part of patient management. Dogs were administered PN at the discretion of the primary clinician. A lipid-free, ready-made solution containing amino acid (59 g/L) and dextrose (100 g/L) was administered intravenously as a constant rate infusion to provide nutritional support. PN was provided for a median of 2.2 days (range 0.5-9.5 days) in the 70 dogs, totaling 168 days of PN. The PN provided a median of 5.5 g/100 kcal of protein (range 1-9.5 g/100 kcal) and a median of 2.2 mg/kg of bodyweight per minute (range 0.8-5.2 mg/kg/min) of glucose, which reflected a median of 57% of the resting energy requirement (range 9-100%). Metabolic complications developed in 43 of 67 dogs where these data were recorded, but the development of hyperkalemia was the only complication associated with a poor outcome (eg, death or euthanasia). Mechanical complications were seen in 28 dogs, and all but one of these occurred when PN was delivered through peripheral catheters. Septic complications were confirmed in 5 dogs. This form of PN is suitable for clinical use and can provide both protein and calories to ill dogs. It was, however, associated with a high rate of complications and requires careful patient monitoring.

TCH-051 Validation of an Automated Compounder Set Up Once a Week For Parenteral Nutrition Solutions

BackgroundOur parenteral nutrition production (PN) decreased after we introduced standard solutions. To keep just a small number of daily PN items cost-effective, we decided to validate a once a week...

The Safety and Efficacy of Parenteral Nutrition Among Pediatric Patients With Burn Injuries*

Although enteral nutrition is the ideal mode of nutritional support following burn injury, it is often interrupted during episodes of severe sepsis and hemodynamic instability, leading to significant energy and protein deficits. Parenteral nutrition is not commonly used in burn centers due to concerns that it will lead to hyperglycemia, infection, and increased mortality. However, parenteral nutrition is often utilized in our burn unit when goal rate enteral nutrition is not feasible.To determine the safety and efficacy of a standardized protein-sparing parenteral nutrition protocol in which glucose infusion is limited to 5-7 mg/kg/hour. Retrospective observational study. Pediatric burn hospital. A retrospective medical record review of all children admitted to our hospital with burns ≥ 30% total body surface area was conducted. Only patients admitted within one week of injury and who survived > 24 hours after admission were included in this study. None. Of the 105 patients who met the inclusion criteria, 96 (91%) received parenteral nutrition or a combination of parenteral nutrition and enteral nutrition at some point during their care. Nine patients received only enteral nutrition. Demographic data were similar between groups. Protein intake was significantly higher in the parenteral nutrition group. Incidence of catheter-related blood infections did not differ between groups. Use of parenteral nutrition was not associated with blood or respiratory infections. Overall mortality rate was low (4%), as most patients (96%) achieved wound closure and were discharged home. Judicious use of parenteral nutrition is a safe and effective means of nutritional support when goal enteral nutrition cannot be achieved. A hypocaloric, high-nitrogen parenteral nutrition solution can reduce energy and protein deficits while minimizing complications commonly associated with parenteral nutrition usage.

Aluminium in parenteral nutrition: a systematic review

Aluminium (Al) toxicity problem in parenteral nutrition solutions (PNS) is decades old and is still unresolved. The aim of this review is to gather updated information about this matter, regarding legislation, manifestations, diagnostics and treatment, patient population at risk and the actions to be taken to limit its accumulation. A structured search using MeSH vocabulary and Title/Abstract searches was conducted in PubMed (http://www.pubmed.gov) up to November 2012. Al is ubiquitous, facilitating its potential for exposure. Nevertheless, humans have several mechanisms to prevent significant absorption and to aid its elimination; therefore, the vast majority of the population is not at risk for Al toxicity. However, when protective gastrointestinal mechanisms are bypassed (for example, parenteral fluids), renal function is impaired (for example, adult patients with renal compromise and neonates) or exposure is high (for example, long-term PNS), Al is prone to accumulate in the body, including manifestations such as impaired neurological development, Alzheimer's disease, metabolic bone disease, dyslipemia and even genotoxic activity. A high Al content in PNS is largely the result of three parenteral nutrient additives: calcium gluconate, inorganic phosphates and cysteine hydrochloride. Despite the legislative efforts, some factors make difficult to comply with the rule and, therefore, to limit the Al toxicity. Unfortunately, manufacturers have not universally changed their processes to obtain a lower Al content of parenteral drug products (PDP). In addition, the imprecise information provided by PDP labels and the high lot-to-lot variation make the prediction of Al content rather inaccurate.

Thrombocytopenia caused by low-dose heparin supplementation of parenteral nutrition solution

TO THE EDITOR: Heparin-induced thrombocytopenia (HIT) is a significant complication of heparin therapy. Risk factors for HIT include the type of heparin used, duration of heparin exposure, and clinical setting. Here, we report a 76-year-old man who presented with life-threatening pulmonary thromboembolism and deep-vein thrombosis, preceded by a dramatic decrease in platelet count 1 week after radical cystectomy for transitional cell bladder carcinoma. He was diagnosed with type II HIT caused by a small amount of unfractionated heparin mixed into his total parenteral nutrition (TPN) solution. One thousand units heparin per day were added to his TPN for 1 week. A heparin-platelet factor-4 antibody enzyme-linked immunosorbent assay of his serum was strongly positive. After cessation of TPN infusion, argatroban was started for thrombosis. His platelet count gradually increased to a normal level, and the thrombosis was treated successfully. This case suggests HIT should be suspected in patients with typical clinical manifestations and risk factors, even if the infused heparin dose is small. Heparin is widely used in a variety of medical therapies from the treatment of life-threatening acute thromboembolisms to the maintenance of indwelling vascular catheter patency. However, heparin therapy is often complicated by thrombocytopenia. The incidence of heparin-induced thrombocytopenia (HIT) in patients who receive heparin including unfractionated heparin and low-molecular-weight heparin is 0.1-5% [1]. There are 2 types of HIT. Type I HIT is a relatively common non-immune reaction that causes an asymptomatic, transient, and mild decrease in platelet count. In contrast, type II HIT is an immune complex disorder involving heparin bound to the platelet-specific chemokine, platelet factor-4 (PF4). These heparin-PF4 complexes activate both platelets and endothelial cells, resulting in platelet consumption and endothelial injury with thrombosis and disseminated intravascular coagulation [2]. Heparin use could go unnoticed if it is not applied as a conventional anticoagulant but rather as a supportive agent to maintain vasc,ular patency. However, unrecognized HIT can lead to life-threatening complications. Therefore, it is important to suspect HIT in patients who develop acute thrombosis or thrombotic tendency preceded by a decrease in platelet count during or soon after heparin therapy, even if the infused amount is small. Immediate discontinuation of heparin administration and initiating alternative anticoagulant therapy are critical for avoiding further thrombosis, even before laboratory results are available [3]. To the best of our knowledge, this is the first report on a patient who experienced type II HIT after low-dose heparin added to his total parenteral nutrition (TPN) for 1 week.

What is our development progress for the treatment outcome of newborn with intestinal atresia and stenosis in a period of 28 years?

Intestinal atresia is a well-recognized cause of bowel obstruction in the newborn. The aim of this study was to examine the serial regarding the intestinal atresia and stenosis patients in a period of 28 years in a developing country and to display our progress in treatment and survival rates today. In this study, a total of 141 intestinal atresia and stenosis cases were retrospectively evaluated. The cases were categorized in two groups as 45 cases before the 1990 (group 1) when it was impossible for total parenteral nutrition (TPN) solutions to be used regularly, without complication and for a long time and 96 cases after 1990 (group 2) when this was possible. While the survival rate before 1990 was 55%, after 1990 it was 94%. As a result, long-term regular TPN usage significantly improved survival in newborns with intestinal atresia and stenosis in a developing country.

Effects of Lipid Emulsion and Multivitamins on the Growth of Microorganisms in Peripheral Parenteral Nutrition Solutions

Background: Blood stream infections caused by Bacillus cereus or Serratia marcescens in patients receiving peripheral parenteral nutrition (PPN) have occasionally been reported in Japan, but these microorganisms are not major causes of blood stream infections in patients receiving total parenteral nutrition via a central venous catheter. In Japan, commercially available PPN solutions contain amino acids, glucose, and electrolytes, but not contain lipid emulsion (LE) and multivitamins (MV). In this study, the effects of LE and MV on the growth of microorganisms such as Bacillus cereus, Serratia marcescens, Staphylococcus aureus, and Candida albicans in PPN solutions were investigated. Methods: A commercial 3% amino acid and 7.5% glucose solution with electrolytes (AF) was used as the base solution to prepare test solutions (LAF, AFV, and LAFV) containing LE, MV, or both. Specifically, 20% LE was added to AF in a ratio of 1:9 to prepare LAF. MV was added to AF and LAF to prepare AFV and LAFV, respectively. A specified number of each microorganism was added to each 100 mL of AF, LAF, AFV, and LAFV in sterile plastic flasks, and all flasks were allowed to stand at room temperature. The number of colony forming units per mL of each microorganism was counted at 0, 24, and 48 hours after the addition of each microorganism. Results: Both Bacillus cereus and Serratia marcescens increased rapidly in AF as well as in LAF, AFV, and LAFV. Staphylococcus aureus did not increased in AF, but increased slightly in LAF and increased rapidly in AFV and LAFV. Candida albicans increased slightly in AF and increased rapidly in LAF, AFV, and LAFV. Conclusions: The results suggest the followings: if microbial contamination occurs, 1) Bacillus cereus and Serratia marcescens can grow rapidly in PPN solutions consisting of amino acids, glucose and electrolytes; 2) Staphylococcus aureus cannot grow without LE and MV, but can grow rapidly with MV; 3) Candida albicans can grow slowly without LE and MV, and the addition of LE or MV accelerates its growth.

The effects of &lt;i&gt;n&lt;/i&gt;-3 polyunsaturated fatty acid-rich total parenteral nutrition on neutrophil apoptosis in a rat endotoxemia

Although recruited neutrophils function as first-line defense to remove bacteria, delayed apoptosis is implicated in persistent inflammation leading to organ injury. Leukotrien B4, n-6 polyunsaturated fatty acids (PUFAs) product, is one of the mediators that delay neutrophil apoptosis. The mechanism of the beneficial effects of supplementation of fish oil-based long-chain n-3 PUFAs in parenteral nutrition for critically ill patients has not been fully understood. One possible mechanism is the less inflammatory n-3 PUFAs products can compete with proinflammatory n-6 PUFAs products for access to the enzymes. The aim of this study was to determine whether n-3 PUFA rich parenteral nutrition may alter the composition of fatty acids in the neutrophil membrane and restore delay of neutrophil apoptosis during endotoxin-induced systemic inflammation in rats. The animals in group 1 were treated with 20% Hicaliq NC-N in Neoparen-2 for three days. The animals in group 2 (referred to as n-6 PUFA-rich parenteral nutrition) were given parenteral nutrition solutions containing 20% soybean oil in Neoparen-2 (n-6/n-3 = 10). The animals in group 3 (referred to as n-3 PUFA-rich parenteral nutrition) were administered parenteral nutrition consisting of 10% soybean oil and 10% fish oil emulsion (n-6/n-3 = 1.3). The n-3/n-6 ratio of the neutrophil membrane was significantly increased in group 3 and was associated with restored lipopolysaccharide-delayed-apoptosis of neutrophils in bone marrow cells and increased production of leukotriene B5 from peritoneal neutrophils stimulated by lipopolysaccharide. Our preliminary results showed that n-3 PUFA-rich parenteral nutrition regulated neutrophil apoptosis and prevented synthesis of pro-inflammatory eicosanoids, explaining the protective effects seen in the clinical setting.